The sight of the eight-year-old little girl and her six-year-old sister heading straight for my office candy jar brought an instant smile to my face. One of the special joys in family medicine is seeing the children I've delivered grow and change.
Their mother had a difficult time getting pregnant for several years because of unpredictable fertility due to polycystic ovary syndrome. When she came to me about her fertility problems I started her on metformin, a medication approved by the Food and Drug Administration for diabetes treatment, but not for polycystic ovary syndrome.
Her menstrual cycles normalized and she became pregnant twice, with a healthy baby girl each time.
Sometimes medications are approved by the FDA for one purpose, but are found by physicians to be useful for other things. Metformin is one such medication.
Doctors are able to prescribe medications for conditions that aren't officially sanctioned by the FDA. This comes as a surprise to many people.
When there is good evidence for such "off-label" treatment, this flexibility is a good thing. However, many off-label uses don't have good evidence behind them. I try to stick with medications and off-label uses that have some evidence behind them.
A recent study4 in the Archives of Internal Medicine estimated that 21% of prescriptions for office-based care in the U.S. are for off-label indications. Seventy-three percent of the off-label uses had little or no scientific support.
Certainly, some drugs that get prescribed off-label do not prove to be useful for patients, but I think many useful things haven't been sufficiently studied. Knowing when such things are useful and appropriate is part of the art of medicine.
Many of these drugs are generic and drug companies no longer have any incentive to do expensive new studies to prove the medications work for more than one problem.
Certain drugs used for children and pregnant women aren't officially approved by the FDA since these groups are difficult to involve in clinical trials. At my office, we treat plenty of these patients every day with medications lacking the approval of the FDA for those uses. We wouldn't have much to treat them with otherwise.
A two-month-old infant in my office with an ear infection presents a particular challenge. I use generic amoxicillin first, but beyond that, treatment of resistant infections often relies on off-label use.
Zithromax, one of the more popular antibiotics in the country, hasn't been approved for children less than six months of age, nor has Cefzil. Still, doctors occasionally use these types of drugs for children under the approved ages.
Patients deserve to be informed when I'm recommending a medication that isn't FDA-approved for their condition. I suspect that isn't done often enough because doctors are so used to off-label prescribing that they don't think enough about it.
I try to explain to my patients where I get my information. I use evidenced-based sources and online peer-reviewed sources of the latest treatments. I look up information together with patients in the exam room. I pay close attention to nationally published and reviewed clinical guidelines for many conditions that I treat. I just spent five hours today reviewing the latest evidenced-based treatments for heart failure as a requirement for maintaining my board certification.
The FDA has compiled a list of medications on its Web site5 where doctors and patients can check for potential problems. It isn't an exhaustive list, however. I always have concern when prescribing any medication, off label or not. Clinical training in medical school and residency help me make judgment calls.
What I try not to do is listen to drug reps, whom I no longer welcome in my office. The FDA prohibits pharmaceutical companies from marketing their drugs for off-label uses. Still, there have been examples of alleged promotion of medications for off-label uses.
The manufacturer of Neurontin, a seizure medication with a narrow FDA indication, was taken to task6 by regulators for marketing off-label uses. Questions have also been raised7 about promotion of off-label uses of Actiq, a narcotic approved for use with cancer pain.
Who is going to pay for use of off-label medications has also been an issue. Recently I prescribed a topical estrogen cream, Premarin, for a 14-year-old boy with recurrent nosebleeds resistant to humidified air and topical antibiotics. It sounds a little odd, but I've had good results with applying estrogen to the nasal membranes to prevent nosebleeds. There is anecdotal experience8 of its effectiveness in my practice and others.
Illinois Medicaid denied the prescription because Premarin was not approved for this use. (The agency, when asked for a comment, said a patient's doctor can submit a special request for approval.) Besides surgery, and waiting with the hope that the bleeds will stop, there really isn't any other treatment to pursue that we haven't already tried.
Despite the challenges and controversies of off-label prescribing, it remains a useful tool in the art of medicine.